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【结 构 式】 
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【分子编号】19239 【品名】diisopropyl [[(1S)-2-hydroxy-1-methylethyl]oxy]methylphosphonate 【CA登记号】 |
【 分 子 式 】C10H23O5P 【 分 子 量 】254.263382 【元素组成】C 47.24% H 9.12% O 31.46% P 12.18% |
合成路线1
该中间体在本合成路线中的序号：(XIV)2) The reaction of the previously described (R)-2-(2-tetrahydropyranyloxy)-1-propanol (III) with benzyl bromide (XI) by means of NaH in DMF, followed by a treatment with Dowex 50X, gives 1-benzyloxy-2(R)-propanol (XII), which is condensed with tosyloxymethylphosphonic acid diisopropyl ester (IX) by means of NaH in THF, yielding 2-benzyloxy-1(R)-methylethoxymethylphosphonic acid diisopropyl ester (XIII). The hydrogenolysis of (XIII) over Pd/C in methanol affords 2-hydroxy-1(R)-methylethoxymethylphosphonic acid diisopropyl ester (XIV), which is tosylated with tosyl chloride/dimethyl-aminopyridine in pyridine to give the expected tosylate (XV). The condensation of (XV) with adenine (VI) by means of Cs2CO3 in hot DMF yields 9-[2(R)-(diisopropoxyphosphorylmethoxy)propyl]adenine (X), which is finally hydrolyzed as before.
| 【1】 Masojídková, M.; Holý, A.; Synthesis of enantiomeric N-(2-phosphonomethoxypropyl) derivatives of purine and pyrimidine bases. I. The stepwise approach. Coll Czech Chem Commun 1995, 60, 7, 1196. |
| 【2】 Sorbera, L.A.; Castañer, J.; (R)-PMPA and Bis(POC)PMPA. Drugs Fut 1998, 23, 12, 1279. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 19228 | (2S)-2-(tetrahydro-2H-pyran-2-yloxy)-1-propanol | 76946-21-9 | C8H16O3 | 详情 | 详情 |
| (V) | 10343 | 9H-Purin-6-amine; 9H-Purin-6-ylamine; Adenine | 73-24-5 | C5H5N5 | 详情 | 详情 |
| (IX) | 19234 | (diisopropoxyphosphoryl)methyl 4-methylbenzenesulfonate | C14H23O6PS | 详情 | 详情 | |
| (X) | 19235 | diisopropyl [[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethyl]oxy]methylphosphonate | C15H26N5O4P | 详情 | 详情 | |
| (XI) | 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 |
| (XII) | 19237 | (2R)-1-(benzyloxy)-2-propanol | C10H14O2 | 详情 | 详情 | |
| (XIII) | 19238 | diisopropyl [[(1S)-2-(benzyloxy)-1-methylethyl]oxy]methylphosphonate | C17H29O5P | 详情 | 详情 | |
| (XIV) | 19239 | diisopropyl [[(1S)-2-hydroxy-1-methylethyl]oxy]methylphosphonate | C10H23O5P | 详情 | 详情 | |
| (XV) | 19240 | (2S)-2-[(diisopropoxyphosphoryl)methoxy]propyl 4-methylbenzenesulfonate | C17H29O7PS | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)
| 【1】 Holy A, Dvorakovs H, Declercq ED, et al. Preparation of antiretroviral enantiomeric nucleotide analogs. WO 9403467 |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 19228 | (2S)-2-(tetrahydro-2H-pyran-2-yloxy)-1-propanol | 76946-21-9 | C8H16O3 | 详情 | 详情 |
| (II) | 19230 | 2-(((S)-1-(benzyloxy)propan-2-yl)oxy)tetrahydro-2H-pyran | C15H22O3 | 详情 | 详情 | |
| (III) | 66832 | (S)-((2-(chloromethoxy)propoxy)methyl)benzene | C11H15ClO2 | 详情 | 详情 | |
| (IV) | 19238 | diisopropyl [[(1S)-2-(benzyloxy)-1-methylethyl]oxy]methylphosphonate | C17H29O5P | 详情 | 详情 | |
| (V) | 19239 | diisopropyl [[(1S)-2-hydroxy-1-methylethyl]oxy]methylphosphonate | C10H23O5P | 详情 | 详情 | |
| (VI) | 19240 | (2S)-2-[(diisopropoxyphosphoryl)methoxy]propyl 4-methylbenzenesulfonate | C17H29O7PS | 详情 | 详情 | |
| (VII) | 10343 | 9H-Purin-6-amine; 9H-Purin-6-ylamine; Adenine | 73-24-5 | C5H5N5 | 详情 | 详情 |
| (VIII) | 19246 | diethyl [[(1S)-2-(6-amino-9H-purin-9-yl)-1-methylethyl]oxy]methylphosphonate | C13H22N5O4P | 详情 | 详情 |